Desta B, Schultz D, Ravel D, Laudignon N, Vanhoutte P M, Boulanger C M
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
J Pharmacol Exp Ther. 1996 Dec;279(3):1077-85.
Experiments were designed to verify whether or not acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm in vivo or in vitro. Rings of left anterior and left circumflex porcine coronary artery, with and without endothelium, were studied in conventional organ chambers for the measurement of isometric force. The donor pigs were divided into two groups: controls and animals fed for 4 weeks with dexfenfluramine. In each group, one-half of the animals underwent balloon denudation of the left anterior descending coronary artery at the beginning of the study. Coronary angiography was performed at the time of denudation and, in all animals, during the 3rd week of the study. Acutely, dexfenfluramine at concentrations higher than 10(-5) M caused contractions which were blunted by the presence of the endothelium and inhibited by indomethacin (an inhibitor of cyclooxygenase). Chronic treatment with dexfenfluramine did not affect coronary diameter and did not alter the response to intracoronary infusion of serotonin. Chronic treatment with dexfenfluramine reduced the contractions of rings without endothelium to serotonin, but not those to norepinephrine or endothelin. It did not affect endothelium-dependent relaxations in the absence or presence of pertussis toxin to serotonin, UK14304 (alpha-2 adrenergic agonist), adenosine diphosphate or aggregating platelets. Chronic treatment with dexfenfluramine did not modify relaxations of rings without endothelium to SIN-1 (nitric oxide donor; the active metabolite of molsidomine) or adenosine diphosphate. These findings do not support the hypothesis that acute or chronic exposure to dexfenfluramine favors the occurrence of coronary vasospasm.
设计实验以验证急性或慢性暴露于右芬氟拉明是否会促进体内或体外冠状动脉痉挛的发生。在传统器官腔室中研究了有内皮和无内皮的猪左前降支和左旋支冠状动脉环，用于测量等长力。供体猪分为两组：对照组和用右芬氟拉明喂养4周的动物。在每组中，一半动物在研究开始时接受左前降支冠状动脉球囊剥脱术。在剥脱时以及所有动物在研究的第3周进行冠状动脉造影。急性情况下，浓度高于10（-5）M的右芬氟拉明会引起收缩，这种收缩在内皮存在时会减弱，并被吲哚美辛（一种环氧化酶抑制剂）抑制。右芬氟拉明的慢性治疗不影响冠状动脉直径，也不改变对冠状动脉内注入5-羟色胺的反应。右芬氟拉明的慢性治疗减少了无内皮环对5-羟色胺的收缩，但对去甲肾上腺素或内皮素的收缩没有影响。在不存在或存在百日咳毒素的情况下，它不影响对5-羟色胺、UK14304（α-2肾上腺素能激动剂）、二磷酸腺苷或聚集血小板的内皮依赖性舒张。右芬氟拉明的慢性治疗不改变无内皮环对SIN-1（一氧化氮供体；吗多明的活性代谢产物）或二磷酸腺苷的舒张。这些发现不支持急性或慢性暴露于右芬氟拉明会促进冠状动脉痉挛发生的假说。
